15-42945216-C-T

Variant names:

• chr15-42945216-C-T
• rs62020698
• NM_174916.3:c.*113G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_174916.3(UBR1):​c.*113G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 1,415,250 control chromosomes in the GnomAD database, including 4,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (363 hom., cov: 33)
  • Exomes 𝑓: 0.079 (4579 hom.)
• Consequence: UBR1 NM_174916.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.174
• Publications: 14 publications found

Genes affected

UBR1 (HGNC:16808): (ubiquitin protein ligase E3 component n-recognin 1) The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, encoded by this gene, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. This leads to the eventual degradation of the substrate protein. The protein described in this record has a RING-type zinc finger and a UBR-type zinc finger. Mutations in this gene have been associated with Johanson-Blizzard syndrome. [provided by RefSeq, Jul 2008]

UBR1 Gene-Disease associations (from GenCC):

• Johanson-Blizzard syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 15-42945216-C-T is Benign according to our data. Variant chr15-42945216-C-T is described in ClinVar as [Benign]. Clinvar id is 1281511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR1	NM_174916.3	c.*113G>A		3_prime_UTR_variant	Exon 47 of 47	ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR1	ENST00000290650.9	c.*113G>A		3_prime_UTR_variant	Exon 47 of 47	1	NM_174916.3	ENSP00000290650.4
UBR1	ENST00000562173.1	n.568G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9350 AN: 152166 Hom.: 363 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0699

GnomAD4 exome AF: 0.0789 AC: 99704 AN: 1262966 Hom.: 4579 Cov.: 18 AF XY: 0.0775 AC XY: 49174 AN XY: 634234

African (AFR) AF: 0.0196 AC: 572 AN: 29130

American (AMR) AF: 0.0677 AC: 2639 AN: 38996

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 1987 AN: 24506

East Asian (EAS) AF: 0.000268 AC: 10 AN: 37288

South Asian (SAS) AF: 0.0212 AC: 1664 AN: 78624

European-Finnish (FIN) AF: 0.0258 AC: 1307 AN: 50666

Middle Eastern (MID) AF: 0.0757 AC: 329 AN: 4346

European-Non Finnish (NFE) AF: 0.0920 AC: 87053 AN: 945882

Other (OTH) AF: 0.0774 AC: 4143 AN: 53528

GnomAD4 genome AF: 0.0614 AC: 9346 AN: 152284 Hom.: 363 Cov.: 33 AF XY: 0.0576 AC XY: 4290 AN XY: 74456

African (AFR) AF: 0.0213 AC: 886 AN: 41572

American (AMR) AF: 0.0831 AC: 1270 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 297 AN: 3472

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5190

South Asian (SAS) AF: 0.0211 AC: 102 AN: 4826

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10614

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0907 AC: 6168 AN: 68010

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

Alfa AF: 0.0710 Hom.: 314

Bravo AF: 0.0651

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	9.3
DANN	Benign	0.62
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs62020698; hg19: chr15-43237414;